BIOCHEMISTRY

Studying the structure and dynamics of biological macromolecules using cryo-EM

The main research focus of the lab is the development of methods for single-particle cryo electron microscopy (cryo-EM), a technique for determining the structure of biological molecules.  In this technique, many hundreds of thousands to millions of images of molecules are taken on an electron microscope. By combining all of the information from these images using image processing techniques, it is possible to visualize the detailed atomic structure of the molecules. This allows us to gain a deeper understanding of how they work, and can be used to design new drugs to target these molecules and ultimately provide therapeutic treatment for disease.

As part of these efforts, we develop cisTEM (www.cistem.org), a software package containing a complete workflow for processing single-particle cryo-EM images within a user-friendly interface.

Cryo-EM image of rotavirus DLPs and the associated 2.6Å structure of rotavirus VP6

Capturing the motion of molecular machines

A strength of cryo-EM is the ability to understand dynamics within the imaged samples.  An insight into the dynamics of proteins further enhances the understanding of their function, and the ability to design drugs to target.  Current methods for understanding the dynamics of large scale and continuous motion within proteins are limited, and a key goal of the lab is to develop improved methods for extracting information from these dynamics.

Cryo-EM images of clathrin cages and their calculated dynamics

SCORE Program | SUPER-G Program